한빛사논문
Suji Choi 1, Keel Yong Lee 1,2, Sean L. Kim1, Luke A. MacQueen1, Huibin Chang1, John F. Zimmerman 1, Qianru Jin 1, Michael M. Peters 1, Herdeline Ann M. Ardoña 1,3, Xujie Liu4,5, Ann-Caroline Heiler 6,7,8, Rudy Gabardi1, Collin Richardson1, William T. Pu 4,9, Andreas R. Bausch 6,7,8,10 & Kevin Kit Parker 1,9,11
1Disease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, USA.
2Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.
3Department of Chemical and Biomolecular Engineering, Samueli School of Engineering, University of California, Irvine, CA, USA.
4Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA.
5Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, China.
6Department of Bioscience, TUM School of Natural Sciences, Technische Universität München, Garching, Germany.
7Center for Functional Protein Assemblies, Technische Universität München, Garching, Germany.
8Center for Organoid Systems(COS), Technische Universität München, Garching, Germany.
9Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
10Max Planck School Matter to Life, Max Planck Schools, Heidelberg, Germany.
11Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Corresponding author : Correspondence to Kevin Kit Parker.
Abstract
Hydrogels are attractive materials for tissue engineering, but efforts to date have shown limited ability to produce the microstructural features necessary to promote cellular self-organization into hierarchical three-dimensional (3D) organ models. Here we develop a hydrogel ink containing prefabricated gelatin fibres to print 3D organ-level scaffolds that recapitulate the intra- and intercellular organization of the heart. The addition of prefabricated gelatin fibres to hydrogels enables the tailoring of the ink rheology, allowing for a controlled sol-gel transition to achieve precise printing of free-standing 3D structures without additional supporting materials. Shear-induced alignment of fibres during ink extrusion provides microscale geometric cues that promote the self-organization of cultured human cardiomyocytes into anisotropic muscular tissues in vitro. The resulting 3D-printed ventricle in vitro model exhibited biomimetic anisotropic electrophysiological and contractile properties.
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